Parenchymal-stromal cell interaction in metabolic diseases  [in Japanese]

Access this Article

Search this Article

Author(s)

    • Ogawa Yoshihiro
    • Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan|CREST, Japan Agency for Medical Research and Development, Tokyo, Japan
    • Suganami Takayoshi
    • Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan|PREST, Japan Science and Technology Agency, Tokyo, Japan
    • Tanaka Miyako
    • Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
    • Itoh Michiko
    • Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan

Abstract

Evidence has suggested that parenchymal-stromal cell interaction is implicated in the development of a variety of metabolic diseases. In obese adipose tissue, saturated fatty acids, which are released as a danger signal from hypertrophied adipocytes, stimulates a pathogen sensor TLR4 in the infiltrating macrophages, thus establishing a vicious cycle that augments adipose tissue inflammation. Histologically, macrophages aggregate to constitute crown-like structures (CLS), where they are thought to scavenge the residual lipid droplets of dead adipocytes. In obese adipose tissue, macrophage-inducible C-type lectin (Mincle) is induced in macrophages constituting CLS, the number of which is correlated with the extent of interstitial fibrosis. Mincle, when activated by an as-yet-unidentified danger signal released from dead or dying adipocytes, may play a key role in adipose tissue inflammation and fibrosis. Free fatty acids, when released from obese visceral fat depots, are transported in large quantities to the liver via the portal vein, where they are accumulated as ectopic fat, thus developing nonalcoholic steatohepatitis (NASH). There is a unique histological feature termed "hepatic CLS (hCLS)" in the NASH liver, where macrophages aggregate to surround dead hepatocytes with large lipid droplets. Notably, the number of hCLS is positively correlated with the extent of liver fibrosis, which suggests that hCLS serves as an origin of hepatic inflammation and fibrosis during the progression from simple steatosis to NASH. We postulate that CLS/hCLS represent the unique microenvironment for parenchymal-stromal cell interaction in metabolic diseases.

Journal

  • Inflammation and Regeneration

    Inflammation and Regeneration 35(4), 167-171, 2015

    The Japanese Society of Inflammation and Regeneration

Codes

Page Top